The long-term goal of this research is to contribute to the understanding of the mechanism of synaptic transmission. The specific aim of the proposed project is to identify a novel protein involved in synaptic transmission by the "forward genetic" methods using Drosophila and to characterize the in vivo function of the molecule using various genetic, molecular biological, and electrophysiological methods. Three Drosophila mutants belonging to a single complementation group display abnormal histamine distribution in photoreceptors and blocked histamine release, suggesting that they are defective in presynaptic mechanisms of the photoreceptor synaptic process. A 3kb cDNA that most likely corresponds to the gene identified by these mutants has been isolated and completely sequenced. It contains an open reading frame which encodes a novel protein of 953 amino acids but is still open at the 5' end. Immediate goals of the project include isolation of cDNA clones with complete open reading frames, demonstration that the cDNA identified does in fact correspond to the gene, and functional analysis of the protein encoded by the cDNA. Since synaptic transmission is a fundamental property of the nervous system and its overall mechanism is conserved among organisms ranging from yeast to humans, the identification of a molecule important for synaptic transmission in Drosophila is likely to contribute to the understanding of the mechanisms of synaptic transmission in general, including that in humans.